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All the primary trial participants do not receive any oral capecitabine, oral lapatinib ditosylate or cixutumumab IV, in conrast all the secondary trial subjects receive these. | INTERVENTION 1:
Diagnostic (FLT PET)
Patients with early stage, ER positive primary breast cancer undergo FLT PET scan at baseline and 1-6 weeks after the start of standard endocrine treatment. The surgery follows 1-7 days after the second FLT PET scan.
Tracer used in the FLT PET (positron emission tomography) scanning procedure: [F18] fluorothymidine.
Positron Emission Tomography: Undergo FLT PET
Laboratory Biomarker Analysis: Correlative studies - Ki67 staining of the tumor tissue in the biopsy and surgical specimen.
INTERVENTION 1:
Arm A
Patients receive oral capecitabine twice daily on days 1-14 and oral lapatinib ditosylate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. lapatinib ditosylate: Given PO and capecitabine: Given PO
INTERVENTION 2:
Arm B
Patients receive capecitabine and lapatinib ditosylate as in arm I. Patients also receive cixutumumab IV over 1-1½ hours on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. cixutumumab: Given IV, lapatinib ditosylate: Given PO and capecitabine: Given PO | Contradiction |
Patients with Platelet count over 100,000/mm³, ANC < 1,700/mm³ and Hemoglobin between 4 to 5 grams per deciliter are eligible for the primary trial. | PATIENT CHARACTERISTICS:
ANC 1,500/mm³
Platelet count 100,000/mm³
Hemoglobin 9.0 g/dL | Contradiction |
Heart-related adverse events were recorded in both the primary trial and the secondary trial. | Adverse Events 1:
Supraventricular tachycardia 1/32 (3.13%)
Adverse Events 1:
Atrial fibrillation 1/752 (0.13%)
Atrial flutter 0/752 (0.00%)
Cardiac failure congestive 1/752 (0.13%)
Left ventricular dysfunction 0/752 (0.00%) | Entailment |
Adult Patients with histologic confirmation of invasive bilateral breast carcinoma (T1 N1 M1) are eligible for the primary trial. | Inclusion Criteria:
Patients with histologic confirmation of invasive breast carcinoma.
Patients greater than or equal to 18 years.
Patients should have T1N1-3M0 or T2-4 N0-3M0.
Patients with bilateral breast cancer are eligible. | Contradiction |
Laser Therapy is in each cohort of the primary trial and the secondary trial, along with neoadjuvant chemotherapy. | INTERVENTION 1:
Laser Therapy Alone
therapist administered laser treatment
laser: therapist administered laser
INTERVENTION 2:
Mld Alone
therapist administered manual lymphatic drainage
manual lymphatic drainage: therapist administered massage therapy
INTERVENTION 1:
Part A Abemaciclib: HR+, HER2+ Breast Cancer
Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants with hormone receptor positive HR+, HER2+ breast cancer receiving concurrent trastuzumab, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
INTERVENTION 2:
Part B Abemaciclib: HR+, HER2- Breast Cancer
Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for in combination with endocrine therapy (ET).
Participants may continue to receive treatment until discontinuation criteria are met. | Contradiction |
Patients must have already participated in a specific clinical study to participate in the primary trial or the secondary trial. | Inclusion Criteria:
Subjects who were confirmed to have a response after receiving at least two courses of weekly paclitaxel therapy and considered to need to continue the therapy by the investigator/subinvestigator among the patients with advanced or recurrent breast cancer who had met the selection criteria and participated in the preceding phase II clinical study
Inclusion Criteria:
The patient must consent to be in the study and must have signed an approved consent form conforming to institutional guidelines
The patient must be 18 years or older.
Core biopsy should definitively demonstrate invasive carcinoma.
Invasive carcinoma should be ER-apha receptor positive
The tumor should be approximately at least 1 cm, to account for variability in imaging and imaging occult disease (physical exam, mammography, ultrasound). We recognize that from time to time because of this variation, there might not be enough tissue available for analysis after surgical excision but this will allow the greatest opportunity to capture as many eligible patients as possible.
Patients in whom surgical excision of the tumor is part of standard of care management
ECOG score of 0 or 1
Negative serum or urine beta-hCG pregnancy test at screening for patients of child-bearing potential (this is routinely done if the patient is premenopausal and having surgery)
Consent to participate in DBBR (RPCI only)
Exclusion Criteria:
Male patients are not eligible for this study
Female patients with inoperable tumors or women with stage 4 disease diagnosed on CT, PET, PET/CT or bone scan.
Patients with diagnosis by FNA cytology only
Pregnant or lactating women
Prior therapy for breast cancer, including irradiation, chemo- immuno- and/or hormonal therapy
Patients receiving any hormonal therapy, e.g. ovarian hormonal replacement therapy, infertility medications etc., are not eligible
Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient from being subjected to surgical excision
Psychiatric or addictive disorders that would preclude obtaining informed consent
Patients known or suspected to have hypercoagulable syndrome or with history of venous or arterial thrombosis, stroke, TIA, or pulmonary embolism
Women with non-invasive disease or microinvasion are not eligible.
Women undergoing neoadjuvant chemotherapy are not eligible
women currently on tamoxifen and raloxifene for prevention are not eligible
Patients shall not receive any herbal/alternative therapies such as flaxseed or soy products or black cohosh.
Patients with a known mutation in p53 (Li Fraumeni Syndrome) | Contradiction |
Patients with Clinical stage II (T2 N1) invasive mammary carcinoma are not eligible for the primary trial. | Inclusion Criteria:
Clinical stage I or II (T1 or T2, N0 or N1) invasive mammary carcinoma
Exclusion Criteria:
Fixed axillary lymph node metastases (N2) | Contradiction |
the primary trial and the secondary trial have Hypnotherapy based interventions, the secondary trial also used pain medication in its intervention. | INTERVENTION 1:
Adjuvant Radiotherapy
Adjuvant radiation was started within 12 weeks of local excision or breast re-excision.
Adjuvant Radiotherapy: Adjuvant radiation therapy
INTERVENTION 1:
Hypnotherapy
Patients randomized to the hypnosis arm of the study will undergo individually three one-hour sessions with a certified hypnotherapist. These sessions will be one week apart. Patients will also be instructed on the use of self-hypnosis techniques to use at home.
INTERVENTION 2:
Gabapentin
Patients randomized to the gabapentin arm will be prescribed 900mg of the drug daily (300 mg by mouth three times daily). | Contradiction |
Adele is an 85 year old woman with Stage II histologically confirmed ER+ breast cancer with an ECOG of 0, she is eligible for the primary trial | Inclusion Criteria:
Must be female with histologically confirmed breast cancer
Stage II-IV disease
ER and/or PR positive
ECOG Performance Status 0-1
Postmenopausal | Entailment |
Only patients in the primary trial receive 40.5 Gy of brachytherapy, patients in the secondary trial receive no radiotherapy whatsoever. | INTERVENTION 1:
Accelerated Intensity Modulated Radiation Therapy (AIMRT)
All patients shall receive a total of 40.5 Gy to the entire breast in 2.7 Gy/fraction x 15 fractions, Monday to Friday for 3 weeks delivered prone in uniform daily doses through IMRT tangent fields. A concurrent boost to the original tumor bed of 0.50 Gy will be delivered.
Accelerated intensity modulated radiation therapy (AIMRT)
INTERVENTION 1:
AeroForm Tissue Expander
AeroForm Tissue Expansion inflation with carbon dioxide by remote control
AeroForm Tissue Expander: The AeroForm Tissue Expander is a breast tissue expander implanted following mastectomy and activated by remote control to release small doses of carbon dioxide from an internal reservoir to fill and inflate the expander. | Contradiction |
Certain drinks are banned for patients undertaking the primary trial. | Inclusion Criteria:
Agrees not to consume grapefruit juice while on the study | Entailment |
Most of the cases of CHF in the primary trial, were in cohort 1. | Adverse Events 1:
Cardiac failure congestive 1/32 (3.13%)
Adverse Events 2:
Cardiac failure congestive 0/20 (0.00%) | Entailment |
Candidates for the primary trial must have a life expectancy over 6 months. | Life expectancy
Not specified | Contradiction |
Patients eligible for the primary trial must live in the USA. | Inclusion Criteria:
Age 52-75 years old;
Identification as Latina/Hispanic/Chicana female;
Residence in Pilsen, Little Village, East Side or South Chicago; | Entailment |
Patients in group 1 of the secondary trial and the primary trial do not receive the same dosage of AIMRT. | INTERVENTION 1:
Placebo
Subjects will be randomly selected to receive saline (placebo), administered to the breast area to cover the intercostal nerves supplying the breast tissue during surgery.
Saline: If randomized to this arm, subjects will receive an intraoperative injection of saline. (2.5 mg/ml)
INTERVENTION 1:
Accelerated Intensity Modulated Radiation Therapy (AIMRT)
All patients shall receive a total of 40.5 Gy to the entire breast in 2.7 Gy/fraction x 15 fractions, Monday to Friday for 3 weeks delivered prone in uniform daily doses through IMRT tangent fields. A concurrent boost to the original tumor bed of 0.50 Gy will be delivered.
Accelerated intensity modulated radiation therapy (AIMRT) | Entailment |
the primary trial administers letrozole for 28 days, whereas the secondary trial administers is intervention over 4 cycles of 21 days. | INTERVENTION 1:
Post-menopausal Women Using Adjuvant Letrozole
Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants
Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.
INTERVENTION 1:
Neratinib 40 mg
Neratinb 40 mg qd
INTERVENTION 2:
Neratinib 80 mg
Neratinib 80 mg qd | Contradiction |
Candidates for the primary trial must have adequate colon and liver function, and must not be currently receiving amiodarone or have received amiodarone in the last 28 day. Renal function is not relevant for inclusion. | Inclusion Criteria:
The following criteria are to be checked at the time of study entry. The patients may only be included in the study if ALL of the following statements are FULLFILLED:
The patient (male or female) is at least 18 years old at the time of signature of the informed consent form.
Written informed consent has been obtained from the patient prior to the performance of any protocol-specific procedure.
The patient is diagnosed with confirmed invasive breast cancer with stage IV disease.
Note: If the metastatic disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology or histology.
The patient has documented disease progression or relapse following at least one prior standard therapy with trastuzumab (alone or in combination with chemotherapy).
Patients with prior lapatinib use are eligible. Furthermore,
The administration of the chemotherapeutic agent(s) should have been stopped for at least 28 days by the time of the first ASCI administration.
The administration of trastuzumab alone could be maintained after chemotherapy, but the last dose of trastuzumab should not have been given less than three weeks before the first ASCI administration.
The patient will not be given trastuzumab during the trial.
For metastatic patients whose disease is ER+ and/or PR+ the following criteria should be met:
Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases).
Rapidly progressing or life threatening disease, as determined by the investigator.
Patients who received hormonal therapy and are no longer benefiting from this therapy.
A tumor lesion from the patient biopsied before or during screening shows either:
Overexpression of the HER2 protein, as determined by immunohistochemistry (IHC, with result IHC 3+) or
Amplification of the HER2 gene as determined by FISH (at least 4 fold i.e. at least 8 copies).
Note: Overexpression/amplification measurements must be performed on a metastatic lesion in all cases where such a lesion is sufficiently easily accessible. If however such a biopsy is not possible, then these measurements can be performed on the primary tumor. Use of the primary tumor is to be documented and justified.
Ten FFPE tissue sections of the tumor on which the HER2 overexpression/amplification has been done -if available-may be requested. These may be used to retrospectively carry out part of the translational research (i.e. analysis of EGF receptor activity and of the presence of immune effector cells, refer to Section 7).
The patient has at least one measurable lesion according to RECIST criteria.
The patient has ECOG status of 0 or 1.
The patient has adequate bone marrow reserve as indicated by:
White blood cell count >/= 3,000/mm3.
Neutrophil count >/= 1,500/mm3.
Platelet count >/= 100,000/mm3.
Hemoglobin levels >/= 10.0 g/dl.
The patient has adequate renal function as shown by the creatinine levels (i.e. within the normal range).
The patient has adequate hepatic function as shown by serum bilirubin levels i.e:
Serum bilirubin levels within the normal limits.
Both AST and ALT levels <1.5 times the ULN. Note: However, for patients with liver metastasis, a serum bilirubin level <1.5 times the ULN and both AST and ALT levels <3 times the ULN will be accepted.
The patient has a baseline Left Ventricular Ejection Fraction (LVEF) measured by MUGA scan equal to or greater than the LLN for the radiology facility.
If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to treatment, have a negative pregnancy test and continue such precautions for two months after completion of the study treatment.
Adequate contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly (when applicable, as mentioned in the product label) for example abstinence, combined or progestogen oral contraceptives, injectable progestogen, implants of levonorgestrel, oestrogenic vaginal ring, percutaneous contraceptive patches or intrauterine device (IUD) or intrauterine system (IUS), vasectomy with documented azoospermia of the sole male partner or double barrier method (condom or occlusive cap plus spermicidal agent).
For azoospermia, "documented" refers to the outcome of the investigator's/ designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records.
Post-menopause: Menopause is the age associated with complete cessation of menstrual cycles, menses, and implies the loss of reproductive potential by ovarian failure. A practical definition accepts menopause after 1 year without menses with an appropriate clinical profile at the appropriate age e.g. > 45 years.
Able to swallow and retain oral medication.
In the view of the investigator, the patient can and will comply with the requirements of the protocol.
Exclusion Criteria:
The following criteria should be checked at the time of study entry. If any apply, the patient must not be included in the study:
The patient has received > 300 mg/m2 doxorubicin (cumulative dose) or > 600 mg/m2 epirubicin (cumulative dose).
The patient is receiving treatment with bisphosphonate UNLESS the biphosphonate treatment was initiated more than three weeks before the first ASCI administration. (See also section 5.3.2.).
The patient has received any investigational or non-registered product (drug or vaccine) other than the study treatment(s) within 30 days preceding the first dose of study treatment, or planned use during the study period.
The patient is currently receiving amiodarone or has received amiodarone in the 6 months prior to screening.
The patient requires concomitant treatment with systemic corticosteroids or any immunosuppressive agents. The use of prednisone, or equivalent, <0.5 mg/kg/day (absolute maximum 40 mg/day), or inhaled corticosteroids or topical steroids is permitted.
The patient has a malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
Patients with ulcerative colitis.
The patient has known coronary artery disease, arrhythmia requiring treatment, clinically significant valvular disease, cardiomegaly on chest X-ray, ventricular hypertrophy (found by ECG) or previous myocardial infarction.
The patient has any acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
The patient has current active hepatic or biliary's disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
The patient presents with autoimmune disease (vitiligo and autoimmune thyroid disease is not an exclusion criterion).
The patient has a known family history of congenital or hereditary immunodeficiency.
The patient has any uncontrolled bleeding disorder or coagulation disorder or thrombocytopenia or pro-thrombotic disorder.
The patient has a history of anaphylaxis or severe allergic reaction to vaccines or unknown allergens.
The patient has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to Lapatinib. These include other anilinoquinazolines, such as gefitinib (Iressa), erlotinib (Tarceva), or other chemically related compounds or excipients.
The patient is known to be positive for the Human Immunodeficiency Virus (HIV).
The patient has (or has had) previous or concomitant malignancies at other sites except effectively treated:
Non-melanoma skin cancers or carcinoma in situ of the cervix
Malignancy that has been in remission for > 2 years and is considered highly likely to have been cured.
The patient has any psychiatric or addictive disorder that may compromise her ability to give informed consent, or to comply with the trial procedures.
The patient has any other condition that in the opinion of the investigator might jeopardize the patient's safety or ability to comply with the requirements of the study.
The patient is pregnant or lactating. | Contradiction |
both the primary trial and the secondary trial administer Bevacizumab to every single HER2+ patient. | INTERVENTION 1:
Arm 1: Yoga Intervention
Yoga Intervention
Yoga: Yoga sessions
INTERVENTION 2:
Arm 2: Educational Wellness Group
Educational Wellness Group
Education: Educational Wellness Group
INTERVENTION 1:
Arm A: Endocrine Therapy (ET)
Endocrine treatment consisting of either letrozole or fulvestrant. Patients will be randomized to receive bevacizumab 15mg/kg every 3 weeks plus endocrine treatment or endocrine treatment as a single agent. The patients will receive the assigned treatment until the progression of the disease, unacceptable toxicity or withdrawal of the consent.
Letrozole
Fulvestrant
INTERVENTION 2:
Arm B: ET With Bevacizumab (ET-B)
Endocrine treatment consisting of either letrozole or fulvestrant. Patients will be randomized to receive bevacizumab 15mg/kg i.v. on day 1 every 3 weeks plus endocrine treatment or endocrine treatment as a single agent. The patients will receive the assigned treatment until the progression of the disease, unacceptable toxicity or withdrawal of the consent.
Letrozole
Bevacizumab
Fulvestrant | Contradiction |
CO2 is utilised as part of the intervention in a single one of the study groups in the primary trial, and not used in either of the study groups in the secondary trial. | INTERVENTION 1:
AeroForm Tissue Expansion
AeroForm Tissue Expansion inflation with carbon dioxide by remote control
AeroForm Tissue Expansion: The AeroForm Patient Controlled Tissue Expander is a breast tissue expander implanted following mastectomy and activated by remote control to release small doses of carbon dioxide from an internal reservoir to fill and inflate the expander.
INTERVENTION 1:
FFDM and DBT
FFDM exam and DBT scan on Siemens MAMMOMAT Inspiration
INTERVENTION 2:
FFDM Only
FFDM exam only | Entailment |
There were no completed suicides in either the primary trial or the secondary trial, however there was one attempt in cohort 1 of the secondary trial. | Adverse Events 1:
Total: 31/116 (26.72%)
Neutropenia 1/116 (0.86%)
Thrombocytopenia 1/116 (0.86%)
Acute myocardial infarction 1/116 (0.86%)
Myocardial infarction 0/116 (0.00%)
Pericardial effusion 0/116 (0.00%)
Abdominal pain 3/116 (2.59%)
Ascites 1/116 (0.86%)
Diarrhoea 3/116 (2.59%)
Gingival bleeding 1/116 (0.86%)
Intestinal haemorrhage 1/116 (0.86%)
Nausea 2/116 (1.72%)
Adverse Events 2:
Total: 24/115 (20.87%)
Neutropenia 1/115 (0.87%)
Thrombocytopenia 0/115 (0.00%)
Acute myocardial infarction 0/115 (0.00%)
Myocardial infarction 1/115 (0.87%)
Pericardial effusion 1/115 (0.87%)
Abdominal pain 0/115 (0.00%)
Ascites 0/115 (0.00%)
Diarrhoea 4/115 (3.48%)
Gingival bleeding 0/115 (0.00%)
Intestinal haemorrhage 0/115 (0.00%)
Nausea 3/115 (2.61%)
Adverse Events 1:
Total: 8/54 (14.81%)
Anaemia 1/54 (1.85%)
Febrile Neutropenia 1/54 (1.85%)
Retinopathy Hypertensive 1/54 (1.85%)
Febrile Infection 1/54 (1.85%)
Postoperative Wound Complication 1/54 (1.85%)
Cardiac Imaging Procedure Abnormal 1/54 (1.85%)
Malignant Melanoma In Situ 1/54 (1.85%)
Suicide Attempt 1/54 (1.85%)
Dyspnoea 1/54 (1.85%) | Entailment |
the primary trial is testing a chemotherapy treatment whereas the secondary trial is testing a physcotherapy course. | INTERVENTION 1:
Lapatinib With Paclitaxel
Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
INTERVENTION 2:
Placebo With Paclitaxel
Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
INTERVENTION 1:
AlloDerm RTU
Participants within this arm will have the acellular dermal matrix AlloDerm RTU implanted at the time of tissue expander placement.
AlloDerm RTU
INTERVENTION 2:
SurgiMend PRS
Participants within this arm will have the acellular dermal matrix SurgiMend PRS implanted at the time of tissue expander placement.
SurgiMend PRS | Contradiction |
At least 4 patients in both cohorts of the primary trial achieved either complete response (CR) or partial response (PR). | Outcome Measurement:
Objective Response Rate (ORR)
An objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR). A patient has best overall response of CR if she had overall response of CR or PR on one visit and met the confirmation criteria per RECIST. ORR is defined as percentage of patients with objective response.
Each patient with measurable disease at baseline was assessed for OR from the sequence of Response Evaluation Criteria in Solid Tumors (RECIST) scan data up to data cut-off. RECIST scans were performed every 12 weeks (+/- 2weeks) from randomization
Time frame: baseline and every 12 weeks (+/- 2weeks) from randomization data up to data cut-off (19th march 2008)
Results 1:
Arm/Group Title: Fulvestrant 250 mg
Arm/Group Description: Fulvestrant 250 mg
Overall Number of Participants Analyzed: 45
Measure Type: Number
Unit of Measure: percentage of participants 11.1
Results 2:
Arm/Group Title: Fulvestrant 250 mg + Loading Dose
Arm/Group Description: Fulvestrant 250 mg + Loading Dose
Overall Number of Participants Analyzed: 51
Measure Type: Number
Unit of Measure: percentage of participants 17.6 | Entailment |
Less than 1/4 patients in the primary trial experienced adverse events. | Adverse Events 1:
Total: 8/24 (33.33%) | Contradiction |
The both Cohorts of the primary trial receive their treatment via Subcutaneous administration. | INTERVENTION 1:
Initial Cohort
Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG Subcutaneous administration 5 doses of 300 micrograms
Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG: All research participants will receive the Mimotope P10s-PADRE/MONTANIDE ISA 51 VG vaccine via subcutaneous (SC) injection following the schedule
INTERVENTION 2:
Escalation Cohort
Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG Subcutaneous administration of 5 doses of 500 micrograms
Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG: All research participants will receive the Mimotope P10s-PADRE/MONTANIDE ISA 51 VG vaccine via subcutaneous (SC) injection following the schedule | Entailment |
the primary trial does not accept patients with grade 1 alopecia. | Exclusion Criteria Subjects who meet any of the following criteria will be excluded from participation in the treatment protocol:
Existing anti-cancer therapy-related toxicities of Grade >/= 2, except that alopecia and Grade 2 neuropathy are acceptable. | Entailment |
Participant in cohort 1 of the primary trial undergo a Mammography, whereas patients in cohort 1 of the secondary trial receive 6 mg Estradiol as supplementation for the Mammography. | INTERVENTION 1:
Mammography Only
For this reporting arm, the interpretation and analysis was done with mammography only.
INTERVENTION 1:
Arm 1 (6 mg Estradiol)
6 mg of estradiol daily (2 mg tid). | Contradiction |
A single patient in the primary trial experienced a clinically significant inflammation of the back of the throat. | Adverse Events 1:
Acute Pharyngitis * 1/63 (1.59%) | Entailment |
More than 5% of the primary trial participants achieved partial response (PR). | Outcome Measurement:
Objective Response (OR)
Objective response (OR) including complete response (CR) and partial response (PR) according to the Response Evaluation Criteria in Solid Tumours (RECIST) criteria .
Time frame: From first dose of study medication to response measurement, up to 34 month
Results 1:
Arm/Group Title: Afatinib 50 mg
Arm/Group Description: Patients received continuous daily dosing with Afatinib 50 mg therapy over 28-day treatment cycles until further disease progression or undue toxicity.
Overall Number of Participants Analyzed: 41
Measure Type: Number
Unit of Measure: Participants 4 | Contradiction |
Both the primary trial and the secondary trial at least partly administer their interventions orally. | INTERVENTION 1:
Suramin and Paclitaxel
Suramin will be infused weekly over 30 minutes. Four hours after the completion of the suramin infusion the 1 hour infusion of paclitaxel will begin.
INTERVENTION 1:
Ipatasertib and Paclitaxel
Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. | Contradiction |
Neutropenia affected the majority of patients in cohort 1 of the primary trial. | Adverse Events 1:
Neutropenia 4/69 (5.80%) | Contradiction |
the primary trial has a shorter time frame than the secondary trial, both of these studies employ the same units of measure in their evaluation. | Outcome Measurement:
Duration of Moderate Neurtopenia Post First Chemotherapy Administration
Number of days In which the patient has had an absolute neutrophil count (ANC) Level < 2.0 x 10^9/L after first cycle of chemotherapy
Time frame: The first of 4, 21 Day Chemotherapy Cycles
Unit of Measure: days 0.6 (1.26)
Outcome Measurement:
Number of Patients With Congestive Heart Failure (CHF) While on Active Treatment
[Not Specified]
Time frame: 6 months
Unit of Measure: participants 0 | Contradiction |
the primary trial is testing a novel radiotracer called 89Zr-trastuzumab to evaluate its use for visualization of HER2+ lesions. | INTERVENTION 1:
HER2-targeted PET/CT
Pts with confirmed HER2- breast cancer will undergo HER2-targeted PET/CT. 89Zr-trastuzumab is a novel radiotracer which allows excellent visualization of HER2+ lesions. 89Zr-pertuzumab is a novel radiotracer which may allow for specific visualization of HER2+ lesions. PET/CT imaging with these novel radiotracers will allow evaluation of all identifiable malignant lesions, rather than evaluation of only single lesions by biopsy. | Entailment |
Participants of the primary trial are assigned an intervention depending on their prior treatments. | INTERVENTION 1:
Neratinib 240, Prior Trastuzumab
Neratinib: 80mg capsules and 40mg coated tablets taken orally in prescribed dose of 240mg daily, as long as tolerated and disease does not worsen in participants with prior trastuzumab treatment.
INTERVENTION 2:
Neratinib 240, No Prior Trastuzumab
Neratinib: 80mg capsules and 40mg coated tablets taken orally in prescribed dose of 240mg daily, as long as tolerated and disease does not worsen in participants with no prior trastuzumab treatment. | Entailment |
the primary trial and the secondary trial use different inclusion criteria for their cohorts, so patients may be eligible for one cohort, but not the other. | Inclusion Criteria:
(Cohort 1) Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) is allowed if distant metastases have been non-progressing (stable or responding) on that regimen for > or = 12 weeks and skin metastases are non-responsive (stable or progressing) as assessed by the investigator.
(Cohort 2) Any concurrent systemic therapy is allowed
Inclusion Criteria:
Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
HER2+ status defined as IHC 3+ staining or in situ hybridization positive
Patients with resistance to trastuzumab
Prior taxane therapy
Patients with an ECOG performance status of 0 - 2
Patients with measurable disease as per RECIST criteria
Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study;
Patients must meet laboratory criteria defined in the study within 21 days prior to randomization
Exclusion Criteria:
Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer
More than three prior chemotherapy lines for advanced disease.
Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
Peripheral neuropathy grade 2 at randomization
Active cardiac disease
History of cardiac dysfunction
Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
Known hypersensitivity to any study medication
Breastfeeding or pregnant | Contradiction |
A patient has recently been receiving Tamoxifen to treat breast cancer, they are excluded from the primary trial. | Exclusion Criteria:
Prior endocrine therapy for any histologically confirmed cancer is not allowed. Prior endocrine therapy that was administered 5 years ago for the prevention of breast cancer in patients with no history of breast cancer is allowed. | Entailment |
Neither the primary trial or NCT0306117 use chemotherapy or radiotherapy in their intervention. | INTERVENTION 1:
Intervention
Text message management prompts: YBCS will receive text message prompts on how to manage hot flashes and vaginal dryness
Text message management prompts
INTERVENTION 2:
Control
Control YBCS will not receive text message prompts on managing hot flashes and vaginal dryness
INTERVENTION 1:
Arm I (Web-Based CPM-DA)
Patients receive a website address, a secure username and password, and instructions for using the web-based CPM-DA.
Internet-Based Intervention: Receive web-based CPM-DA
Survey Administration: Ancillary studies
INTERVENTION 2:
Arm II (Usual Care)
Patients undergo usual care available to patients considering CPM and receive information from a medical oncologist about CPM.
Survey Administration: Ancillary studies | Entailment |
Agatha had her 50th birthday last week, she has a histologically confirmed adenocarcinoma of the breast, with no evidence of metastatic disease. She is eligible for the primary trial but not the secondary trial. | Inclusion Criteria:
female patients 18-70 years of age;
Inclusion Criteria:
Age 52-75 years old; | Entailment |
several patients in cohort 1 of the primary trial Preferred oral tablets as a Method of Drug Administration. | Outcome Measurement:
Percentage of Participants by Preferred Method of Drug Administration
The preferred method of drug administration (IV or SC Herceptin) was assessed in trial-specific telephone interviews with each study participant. Participants were asked, "All things considered, which method of administration did you prefer?" at the end of the crossover period (Week 24). The percentage of participants who preferred each method of drug administration was reported.
Time frame: Week 24
Results 1:
Arm/Group Title: Cohort 1: SC (SID) Then IV Herceptin
Arm/Group Description: Participants received Herceptin on Day 1 of each 3-week cycle for 18 cycles. During Cycles 1 to 4 of the crossover period, SC Herceptin was administered via SID, and during Cycles 5 to 8, IV Herceptin was given. In the continuation period, participants received IV Herceptin for up to 10 remaining cycles. Administration was performed by HCP. Those with at least 2 treatment cycles remaining of the 18-cycle treatment course after the crossover period were offered the opportunity to self-administer SC Herceptin via SID under the direction of a trained HCP. The SC dose was 600 mg for all cycles where SC Herceptin was given, and the IV dose was 6 mg/kg for all cycles where IV Herceptin was given.
Overall Number of Participants Analyzed: 117
Measure Type: Number
Unit of Measure: percentage of participants SC Herceptin: 95.7
IV Herceptin: 4.3
No Preference: 0.0 | Contradiction |
In the primary trial cohort 2 had more patients with Leukopenia than cohort 1, whereas in the secondary trial cohort 1 had more than cohort 2. Cohort 1 of the primary trial had the highest proportion of patients with leukopenia. | Adverse Events 1:
Leukopenia 0/42 (0.00%)
Adverse Events 2:
Leukopenia 2/61 (3.28%)
Adverse Events 1:
LEUKOPENIA 2/145 (1.38%)
Adverse Events 2:
LEUKOPENIA 0/144 (0.00%) | Contradiction |
There were 7 more cases of Anaemia and 1 more case of Disseminated intravascular coagulation in cohort 1 of the primary trial compared to cohort 2. | Adverse Events 1:
Total: 158/482 (32.78%)
Anaemia 7/482 (1.45%)
Disseminated intravascular coagulation 1/482 (0.21%)
Adverse Events 2:
Total: 37/238 (15.55%)
Anaemia 2/238 (0.84%)
Disseminated intravascular coagulation 0/238 (0.00%) | Contradiction |
There are several types of surgical and therapeutic treatments which are banned for patients wanting to take part in the primary trial. | PRIOR CONCURRENT THERAPY:
No prior thoracic or cardiac surgery
No prior ipsilateral chest tube placement
Contralateral chest tube placement allowed
No prior neoadjuvant chemotherapy
No prior radiotherapy to the mediastinum | Entailment |
The shortest PFS in the Talazoparib group of the primary trial was over a month shorter than the Median PFS for that group. | Outcome Measurement:
Progression-Free Survival (PFS): Independent Radiological Facility (IRF) Assessment
IRF assessed PFS was defined as time (in months) from randomization until the date of first documented radiologic progressive disease per response evaluation criteria in solid tumors (RECIST) version 1.1 or death from any cause, whichever occurs first. As per RECIST v1.1, progression defined as 1) for target lesions: at least a 20% increase in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), the absolute increase in the sum has to be at least 5 millimeter (mm); 2) for non-target lesions: unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions; 3) and/or appearance of one or more new lesions. The analysis was performed by Kaplan-Meier method.
Time frame: Baseline until radiologic progressive disease or death due to any cause (up to maximum duration of 36.9 months)
Results 1:
Arm/Group Title: Talazoparib
Arm/Group Description: Participants received talazoparib 1 mg, orally, once daily until radiographic disease progression as determined by the central IRF, unacceptable toxicity, consent withdrawal, physician's decision to terminate treatment, or sponsor's decision to terminate the trial (up to a maximum of 70.2 months). One cycle was of 21 days.
Overall Number of Participants Analyzed: 287
Median (95% Confidence Interval)
Unit of Measure: months 8.6 (7.2 to 9.3) | Entailment |
Participants in group 2 of the primary trial receive taping to anastomosis regions., but no Complex Decongestive Physiotherapy. | INTERVENTION 1:
Decongestive Physiotherapy
This group received Complex Decongestive Physiotherapy.
Decongestive Physiotherapy: This group received CDP, which include MLD, short-stretch bandages, lymph-reducing exercises, and skin care. MLD was applied to the anterior trunk, posterior trunk, and the base of the neck, progressing to the affected limb. Short-stretch bandages were applied in multiple layers after MLD. A low pH skin lotion was applied prior to bandaging and then stockinette was placed on the arm. The fingers and the hand were wrapped in gauze. A layer of cotton was wrapped around the arm. Bandages (6, 8 and/or 10cm) were sequentially applied in a spiral fashion around the limb with the smallest bandage starting at the hand. The most compression was at the most distal points and gradually decreased proximally. Exercises were done by patients to improve mobility and enhance lymphatic flow.
INTERVENTION 2:
Decongestive Physiotherapy Plus Taping
This group received Complex Decongestive Physiotherapy, and also applying taping to anastomosis regions.
Decongestive Physiotherapy plus taping: This group received CDP as same protocol of active comparator. In addition, taping was applied to anterior and posterior axillo-axillary anastomosis and axillo-inguinal anastomosis. The tape was started on the unaffected side and strips of tape were applied so as to reach the affected side regarding anterior and posterior axillo-axillary anastomosis. For axillo-inguinal anastomosis, the tape was started in the inguinal region of the affected side and strips of tape were applied so that they reached the axillary region. | Contradiction |
None of the patients in cohort 1 of the primary trial had a platlet deficiency, and none of the patients in cohort 2 had Pyrexia. | Adverse Events 1:
Total: 17
Anaemia 2/52 (3.85%)
Febrile neutropenia 4/52 (7.69%)
Pancytopenia 1/52 (1.92%)
Thrombocytopenia 0/52 (0.00%)
Abdominal pain 1/52 (1.92%)
Constipation 1/52 (1.92%)
Pyrexia 2/52 (3.85%)
Hepatic failure 1/52 (1.92%)
Hyperbilirubinaemia 1/52 (1.92%)
Device related infection 1/52 (1.92%)
Pneumonia 2/52 (3.85%)
Sepsis 1/52 (1.92%)
Adverse Events 2:
Total: 7
Anaemia 0/21 (0.00%)
Febrile neutropenia 1/21 (4.76%)
Pancytopenia 0/21 (0.00%)
Thrombocytopenia 1/21 (4.76%)
Abdominal pain 0/21 (0.00%)
Constipation 0/21 (0.00%)
Pyrexia 1/21 (4.76%)
Hepatic failure 0/21 (0.00%)
Hyperbilirubinaemia 0/21 (0.00%)
Device related infection 0/21 (0.00%)
Pneumonia 0/21 (0.00%)
Sepsis 0/21 (0.00%) | Contradiction |
The adverse events in the primary trial where all equally prevalent, whereas in the secondary trial, alcohol poisoning was reported as the most common event. | Adverse Events 1:
Total: 8/29 (27.59%)
Leukopenia [1]1/29 (3.45%)
Thrombocytopenia [1]1/29 (3.45%)
Abscess [1]1/29 (3.45%)
Breast Abscess 1/29 (3.45%)
Fever/Sepsis [1]1/29 (3.45%)
Neutropenic Fever [2]1/29 (3.45%)
Peripheral Neuropathy [1]1/29 (3.45%)
Seizure/Syncope [1]1/29 (3.45%)
Hematuria [1]1/29 (3.45%)
UTI [1]1/29 (3.45%)
Shortness of breath [1]1/29 (3.45%)
Adverse Events 1:
Total: 7/9 (77.78%)
Febrile Neutropenia1/9 (11.11%)
Neutropenia1/9 (11.11%)
Tachycardia1/9 (11.11%)
Hematemesis1/9 (11.11%)
Small Bowel Obstruction1/9 (11.11%)
Pneumonia1/9 (11.11%)
Hypokalemia1/9 (11.11%)
Alcohol Poisoning1/9 (11.11%)
Progressive Disease4/9 (44.44%) | Contradiction |
There were only 3 adverse events in the primary trial which occurred more than twice. | Adverse Events 1:
Total: 10/71 (14.08%)
ATRIAL FIBRILLATION 1/71 (1.41%)
CARDIAC TAMPONADE 1/71 (1.41%)
PERICARDIAL EFFUSION 1/71 (1.41%)
SUPRAVENTRICULAR TACHYCARDIA 1/71 (1.41%)
DIARRHOEA 1/71 (1.41%)
NAUSEA 1/71 (1.41%)
VOMITING 1/71 (1.41%)
CHEST PAIN 1/71 (1.41%)
PNEUMONIA 1/71 (1.41%)
MALIGNANT PLEURAL EFFUSION 1/71 (1.41%)
HEPATIC ENCEPHALOPATHY 1/71 (1.41%) | Contradiction |
Most patients in the Letrozole group of the primary trial had a decreased Bone Mineral Density of the Lumbar Spine after 24 months. | Outcome Measurement:
Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4)
Lumbar spine (L2-L4) BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. The primary scanning site was the lumbar spine (L2 to L4) and the secondary scanning site was the total hip. All DXA scans were evaluated by a central reader.
Time frame: Baseline, 24 months
Results 1:
Arm/Group Title: Letrozole
Arm/Group Description: 2.5 mg once daily (q.d.)orally for 5 years
Overall Number of Participants Analyzed: 63
Median (Full Range)
Unit of Measure: Percent Change -4.63 (-14.21 to 4.32)
Results 2:
Arm/Group Title: Tam-Let
Arm/Group Description: 20 mg Tamoxifen once daily (q.d.) orally for 2 years followed by Letrozole 2.5 mg q.d. orally for 3 years.
Overall Number of Participants Analyzed: 68
Median (Full Range)
Unit of Measure: Percent Change 0.37 (-6.98 to 15.21) | Entailment |
In the primary trial cohort 1 patients must have failed or be intolerant to standard therapy, or have no standard therapy available, and cohort 2 patients must respond well to standard therapy. | INTERVENTION 1:
Monotherapy: Alobresib 0.6 mg
Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
INTERVENTION 2:
Monotherapy: Alobresib 1.4 mg
Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD. | Contradiction |
the primary trial and the secondary trial do not have any overlapping inclusion criteria, apart from the mimimum age limit of 18. | Inclusion Criteria:
Previous participation in study 971-ONC-0028-080.
Exclusion Criteria:
Subjects who had not previously participated in study 971-ONC-0028-080.
DISEASE CHARACTERISTICS:
Diagnosis of breast cancer at high risk for recurrence, defined by one of the following:
Stage IV that is free of all known disease after eradication by surgery, radiotherapy, or chemotherapy
May or may not have elevated CA 15-3 or CEA levels
Stage I, II, or III previously treated with adjuvant chemotherapy and clinically free of identifiable disease, but have rising CA 15-3 or CEA levels
Rising CA 15-3 and CEA defined as a prior normal level increased on 2 consecutive occasions at least 2 weeks apart
For patients with a significant history of smoking who have a chronically elevated CEA (less than 15), CEA must be increased at least 1.5 times the uppermost chronic value on 2 consecutive occasions at least 2 weeks apart
Stage III and completed adjuvant therapy no more than 24 months ago
Recurrence in the ipsilateral axilla after lumpectomy and/or axillary dissection or modified radical mastectomy
Recurrence in the ipsilateral breast after lumpectomy and/or axillary dissection
Stage II with at least 4 positive axillary nodes and completed adjuvant therapy no more than 24 months ago
Stage IV that is stable on hormonal therapy
Hormone receptor status:
Not specified
PATIENT CHARACTERISTICS:
Age:
18 and over
Sex:
Male or female
Menopausal status:
Not specified
Performance status:
Karnofsky 80-100%
Life expectancy:
Not specified
Hematopoietic:
Lymphocyte count at least 500/mm^3
WBC at least 3,000/mm^3
Hepatic:
AST no greater than 1.5 times upper limit of normal (ULN)
Alkaline phosphatase no greater than 1.5 times ULN
Renal:
Creatinine no greater than 1.5 times ULN
Cardiovascular:
No clinically significant New York Heart Association class III or IV cardiac disease
Other:
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception
No prior seafood allergy
No known prior immunodeficiency or autoimmune disease
No other active cancer except basal cell or squamous cell skin cancer
PRIOR CONCURRENT THERAPY:
Biologic therapy:
At least 6 weeks since prior immunotherapy
No prior vaccine with any of the antigens in this study
Chemotherapy:
See Disease Characteristics
At least 4 weeks since prior chemotherapy
No concurrent chemotherapy
Endocrine therapy:
See Disease Characteristics
Radiotherapy:
See Disease Characteristics
At least 4 weeks since prior radiotherapy
No concurrent radiotherapy
Surgery:
See Disease Characteristics
At least 4 weeks since prior surgery
Concurrent surgery for local recurrence allowed if patient remains disease free | Contradiction |
1 patient in the primary trial had toxic hepatitis. | Adverse Events 1:
Hepatotoxicity 1/112 (0.89%) | Entailment |
the secondary trial is testing for the DLT of its interventions, whereas the primary trial is evaluating the efficacy of lymph node detection through the use of SentiMag and SiennaXP. | Outcome Measurement:
Number of Participants With Detected Lymph Nodes
The proportion of lymph nodes detected intraoperatively by SentiMag and SiennaXP in relation the proportion of lymph nodes detected by the combination of Technetium Sulfur Colloid and Isosulfan blue dye
Outcome Measurement:
Number of Participants With Dose Limiting Toxicity (DLT) | Entailment |
Participants of the primary trial must be older than 18, have histologically confirmed stage 4 breast cancer, ECOG<2 and a life expectancy exceeding 6 months. | Inclusion Criteria:
Histologically confirmed Stage IV breast cancer
ECOG performance status 0 or 1
Estimated life expectancy of greater than or equal to 6 months
18 years of age or older | Entailment |
All the primary trial participants receive the same dose of Letrozole, and all patients in the secondary trial are administered the same dose of Tamoxifen. | INTERVENTION 1:
Letrozole
Letrozole 2.5 mg/day for 3 years
INTERVENTION 2:
Letrozole + Zoledronic Acid
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
INTERVENTION 1:
Tamoxifen
Tamoxifen 20mg orally daily for 5 years
INTERVENTION 2:
Ovarian Function Suppression
Tamoxifen 20mg orally daily or Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)
Note: Data were collected separately for the T+OFS and E+OFS participants in the parent study, IBCSG 24-02 (SOFT). The sample size for this Co-SOFT substudy was small, so the analysis plan was revised to pre-specify collective analysis for all patients receiving OFS. | Contradiction |
There were 2 cases of severe back pain observed in the primary trial. | Adverse Events 1:
Total: 3/25 (12.00%)
Anemia 0/25 (0.00%)
Sinus tachycardia 0/25 (0.00%)
Pericardial effusion 1/25 (4.00%)
Gastrointestinal disorders - Other, specify -stomatitis) 0/25 (0.00%)
Vomiting 1/25 (4.00%)
Fever 0/25 (0.00%)
Injection site reaction 1/25 (4.00%)
Catheter related infection 0/25 (0.00%)
Activated partial thromboplastin time prolonged 0/25 (0.00%)
Adverse Events 2:
Total: 2/23 (8.70%)
Anemia 1/23 (4.35%)
Sinus tachycardia 1/23 (4.35%)
Pericardial effusion 0/23 (0.00%)
Gastrointestinal disorders - Other, specify -stomatitis) 1/23 (4.35%)
Vomiting 0/23 (0.00%)
Fever 1/23 (4.35%)
Injection site reaction 1/23 (4.35%)
Catheter related infection 1/23 (4.35%)
Activated partial thromboplastin time prolonged 1/23 (4.35%) | Contradiction |
Across all cohorts of the secondary trial and the primary trial there was only a single recorded case of Myocarditis and Thrombosis. | Adverse Events 1:
Total: 3/73 (4.11%)
Chest Pain - cardiac 1/73 (1.37%)
Myocarditis 1/73 (1.37%)
Pericarditis 1/73 (1.37%)
Ventricular tachycardia 1/73 (1.37%)
Skin infection 0/73 (0.00%)
Dermatitis radiation 0/73 (0.00%)
Dyspnea 1/73 (1.37%)
Adverse Events 2:
Total: 3/70 (4.29%)
Chest Pain - cardiac 0/70 (0.00%)
Myocarditis 0/70 (0.00%)
Pericarditis 0/70 (0.00%)
Ventricular tachycardia 0/70 (0.00%)
Skin infection 2/70 (2.86%)
Dermatitis radiation 1/70 (1.43%)
Dyspnea 0/70 (0.00%)
Adverse Events 1:
Total: 4/43 (9.30%)
Hemoglobin [1]1/43 (2.33%)
Hemorrhage/Bleeding [2]1/43 (2.33%)
Neutrophils/granulocytes (ANC/AGC) [3]1/43 (2.33%)
Platelets [4]1/43 (2.33%)
Anorexia [5]1/43 (2.33%)
Sodium, serum-low (hyponatremia) [1]1/43 (2.33%)
Thrombosis/thrombus/embolism [6]2/43 (4.65%) | Contradiction |
Participants in cohort 1 of the primary trial weighing less than 45 kg receive 5 million units/m^2 less of IL-2, than participants over 45 kg, but all participants will be administered Methylprednisolone 3 times per week for 6 doses. | INTERVENTION 1:
Arm 1: CsA
Fludarabine: Administered intravenously, 25 mg/m^2, days -6 through -2 (5 days).
Cyclophosphamide: Administered intravenously, 60 mg/kg, days -5 and -4.
Cyclosporine (CsA): Administered intravenously, 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Natural Killer cells: Administered by infusion over less than 1 hour; no more than 8.0 x 10^7 cells/kg will be given.
Interleukin- 2 (IL-2): Given subcutaneously at 9 million units 3 times a week for a total of 6 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, IL-2 will be given at 5 million units/m^2 3 times per week for 6 doses). | Contradiction |
One patient in the primary trial had abnormally low red blood cells, white blood cells, and platelets. | Pancytopenia * 1/56 (1.79%) | Entailment |
The adverse events in the primary trial where all equally prevalent, whereas in the secondary trial, progression of disease was reported as the most common event. | Adverse Events 1:
Total: 8/29 (27.59%)
Leukopenia [1]1/29 (3.45%)
Thrombocytopenia [1]1/29 (3.45%)
Abscess [1]1/29 (3.45%)
Breast Abscess 1/29 (3.45%)
Fever/Sepsis [1]1/29 (3.45%)
Neutropenic Fever [2]1/29 (3.45%)
Peripheral Neuropathy [1]1/29 (3.45%)
Seizure/Syncope [1]1/29 (3.45%)
Hematuria [1]1/29 (3.45%)
UTI [1]1/29 (3.45%)
Shortness of breath [1]1/29 (3.45%)
Adverse Events 1:
Total: 7/9 (77.78%)
Febrile Neutropenia1/9 (11.11%)
Neutropenia1/9 (11.11%)
Tachycardia1/9 (11.11%)
Hematemesis1/9 (11.11%)
Small Bowel Obstruction1/9 (11.11%)
Pneumonia1/9 (11.11%)
Hypokalemia1/9 (11.11%)
Alcohol Poisoning1/9 (11.11%)
Progressive Disease4/9 (44.44%) | Entailment |
Less than 5% of cohort 1 of the primary trial had High blood sugar, 0% of the secondary trial patients were recorded as having High blood sugar. | Adverse Events 1:
Total: 6/22 (27.27%)
Thrombocytopenia 1/22 (4.55%)
leucocytopenia 1/22 (4.55%)
neutropenia 1/22 (4.55%)
papilledema 1/22 (4.55%)
Nausea 1/22 (4.55%)
hyperglycemia 1/22 (4.55%)
Adverse Events 1:
Total: 24/101 (23.76%)
LYMPHADENOPATHY 0/101 (0.00%)
FEBRILE NEUTROPENIA 20/101 (0.00%)
ATRIAL FIBRILLATION 1/101 (0.99%)
ARRHYTHMIA 20/101 (0.00%)
CARDIAC FAILURE 22/101 (1.98%)
CARDIAC FAILURE CONGESTIVE 20/101 (0.00%)
CORONARY OSTIAL STENOSIS 20/101 (0.00%)
LACRIMAL DISORDER 0/101 (0.00%)
BLINDNESS 21/101 (0.99%)
GASTRIC ULCER 1/101 (0.99%)
NAUSEA 1/101 (0.99%)
Adverse Events 2:
Total: 22/103 (21.36%)
LYMPHADENOPATHY 1/103 (0.97%)
FEBRILE NEUTROPENIA 21/103 (0.97%)
ATRIAL FIBRILLATION 1/103 (0.97%)
ARRHYTHMIA 21/103 (0.97%)
CARDIAC FAILURE 20/103 (0.00%)
CARDIAC FAILURE CONGESTIVE 21/103 (0.97%)
CORONARY OSTIAL STENOSIS 21/103 (0.97%)
LACRIMAL DISORDER 1/103 (0.97%)
BLINDNESS 20/103 (0.00%)
GASTRIC ULCER 0/103 (0.00%)
NAUSEA 0/103 (0.00%) | Entailment |
Radiotherapy and healing touch therapy is used in all cohorts of the primary trial and the secondary trial. | INTERVENTION 1:
Radiotherapy/Supportive Care (A)
Patients receive radiotherapy and healing touch therapy from a healing-touch therapist once a week for the duration of their radiotherapy
INTERVENTION 2:
Control ARM (B)
Patients receive radiotherapy and sham healing touch therapy from a sham healing-touch therapist once a week for the duration of their radiotherapy
INTERVENTION 1:
Participants With Stage 0-III Breast Cancer
Women with Stage 0-III breast cancer, treated with breast conserving surgery or mastectomy and clear margins, will receive 15 doses of radiation over three weeks.
Hypofractionated Simultaneous Integrated Boost Radiotherapy: Participants will receive radiotherapy treatments to the whole breast or chest wall to a dose of 2.66 Gy per day x 15 fractions simultaneously with a boost treatment. The boost treatment will be given on the same days as the whole breast treatment. The lumpectomy cavity + scar (in lumpectomy patients) or chest wall scar (mastectomy patients) will receive 0.54 Gy per day x 15 fractions. | Contradiction |
There was 38% more patients with DLT in cohort 2 of the primary trial than in cohort 1. | Outcome Measurement:
Number of Participants With Dose Limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)
The following events, if considered to be study-treatment-related by the Investigator, were considered a DLT:
Hematologic:
Grade 4 neutropenia lasting 8 days;
Febrile neutropenia Grade 3 or Grade 4; or
Grade 4 thrombocytopenia requiring platelet transfusion, or Grade 3 thrombocytopenia with bleeding
Non-hematologic:
Grade 4 toxicity;
Grade 3 symptomatic hepatic toxicities lasting >48 hours, or Grade 3 asymptomatic hepatic toxicities lasting 7 days; or
Grade 3 non-hematologic, non-hepatic organ toxicity, with exceptions
Other:
Any treatment delays for 14 days due to unresolved toxicity;
Grade 5 treatment-related adverse event (AE);
A dose reduction of study treatment during the DLT evaluation period.
Time frame: Cycle 1 Day 1 through end of Cycle 3 and Cycle 6 Day 1 through end of Cycle 7 (Up to ~150 days from first dose of first combination regimen); Each cycle was 21 days.
Results 1:
Arm/Group Title: Cohort A: KNp / KAC
Arm/Group Description: Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Overall Number of Participants Analyzed: 10
Measure Type: Count of Participants
Unit of Measure: Participants 2 20.0%
Results 2:
Arm/Group Title: Cohort B: KNpCb (Regimen 1) / KAC
Arm/Group Description: Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Overall Number of Participants Analyzed: 10
Measure Type: Count of Participants
Unit of Measure: Participants 4 40.0% | Contradiction |
In total there were 5x more adverse events in cohort 1 of the primary trial, than in cohort 2. | Adverse Events 1:
Total: 4/26 (15.38%)
Febrile neutropenia * 1/26 (3.85%)
Gastric volvulus * 20/26 (0.00%)
General Malaise * 21/26 (3.85%)
Hospitalisation for intrapleuric chemotherapy and thoracentesis * 21/26 (3.85%)
Acute renal failure * 21/26 (3.85%)
Adverse Events 2:
Total: 1/28 (3.57%)
Febrile neutropenia * 0/28 (0.00%)
Gastric volvulus * 21/28 (3.57%)
General Malaise * 20/28 (0.00%)
Hospitalisation for intrapleuric chemotherapy and thoracentesis * 20/28 (0.00%)
Acute renal failure * 20/28 (0.00%) | Contradiction |
the primary trial and the secondary trial are not studying PFS, PBR or DLTs. | Outcome Measurement:
Concordance of Blue Dye and Lymphoseek
The proportion of lymph nodes detected intraoperatively by blue dye that were also detected by Lymphoseek.
Time frame: Surgery after injections of Lymphoseek and blue dye
Outcome Measurement:
Patient Benefit Rate at 12 Weeks
Percentage of patients with patient benefit at week 12. Patient benefit was defined by the absence of central nervous system (CNS) disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in addition to no tumour-related worsening of the neurological signs and symptoms (NSS), no tumour-related increase in corticosteroid dosage and no progression of extra CNS disease according to RECIST 1.1
Time frame: 12 weeks from randomisation | Contradiction |
Patients with at most stage 3 cancer are eligible for the secondary trial and the primary trial. | Evidence of metastatic involvement (stage IV disease)
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed primary adenocarcinoma of the breast
Locally recurrent or metastatic disease
Must have HER-2-negative breast cancer or, if HER-2-positive, must be unable to receive trastuzumab (Herceptin®) or have previously received trastuzumab in the past
Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm by conventional techniques or as > 10 mm by spiral CT scan.
No known CNS disease
Hormone receptor status not specified
PATIENT CHARACTERISTICS:
Inclusion criteria:
Postmenopausal status not specified
ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
Life expectancy > 12 weeks
WBC 3,000/mcL
Absolute neutrophil count 1,500/mcL
Platelet count 100,000/mcL
Total bilirubin normal
AST and ALT 2.5 times upper limit of normal (ULN)
Alkaline phosphatase 2.5 times ULN (unless bone metastasis is present in the absence of liver metastasis)
Creatinine 1.5 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other concurrent malignancies within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
Exclusion criteria:
Pre-existing neuropathy grade 1
Uncontrolled intercurrent illness including, but not limited to, any of the following:
Ongoing or active infection
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Serious, non-healing wound, ulcer, or bone fracture
Psychiatric illness/social situations that would limit compliance with study requirements
Inadequately controlled hypertension (defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg on antihypertensive medications)
History of hypertensive crisis or hypertensive encephalopathy
New York Heart Association class II-IV congestive heart failure
History of myocardial infarction or unstable angina within the past 6 months
History of stroke or transient ischemic attack within the past 6 months
Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
Symptomatic peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Significant traumatic injury within the past 28 days
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
Proteinuria, as demonstrated by either urine protein:creatinine ratio 1.0 OR urine dipstick for proteinuria 2+
Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline must demonstrate 24-hour urine protein 1g
History of allergy or hypersensitivity to paclitaxel albumin-stabilized nanoparticle formulation, paclitaxel, bevacizumab, carboplatin, albumin, drug product excipients, or chemically similar agents
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
Recovered from all prior therapy
No prior chemotherapy for locally recurrent or metastatic disease
Prior neoadjuvant or adjuvant chemotherapy allowed
More than 1 week since prior core biopsy or other minor surgical procedure, excluding placement of a vascular access device
More than 4 weeks since prior and no concurrent major surgical procedure or open biopsy
More than 4 weeks since prior radiotherapy
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
At least 1 year since prior taxane regimen
No other concurrent investigational agents
Concurrent anticoagulation allowed, provided the following criteria are met:
Stable dose of warfarin or low molecular weight heparin
INR within desired range (2-3)
No evidence of active bleeding or coagulopathy
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent radiotherapy, chemotherapy, immunotherapy, or antitumor hormonal therapy | Contradiction |
Patients with a prior malignancy of skin cancer are excluded from the primary trial. | EXCLUSION CRITERIA (Patient Characteristics):
Other prior malignancies except skin cancer | Contradiction |
None of the patients in Cohort 1 of the primary trial suffered from Hypotension. | Adverse Events 1:
Hypotension 0/50 (0.00%) | Entailment |
Only White and Asian patients are eligible for both the primary trial and the secondary trial. | Inclusion Criteria:
Diagnosis of breast cancer
Part 1 only: Surgery for breast cancer within the past eight weeks (mastectomy or lumpectomy with either sentinel or axillar dissection), including those women with a history of previous surgery for breast cancer, radiation therapy or chemotherapy
Part 2 only: Completion of surgery and radiation therapy for breast cancer within the past six weeks.
Home access to internet from stationary computer, lab top or tablet
Ability to use internet
Ability to read and understand Danish
Exclusion Criteria:
Surgery for breast cancer with immediate breast reconstruction
Diagnosis of primary lymphedema
Metastatic or inflammatory breast cancer
Planned use of chemotherapy within the next 6 weeks
Surgical complications: infection, drainage issues, seroma, hematoma
Severe physical, cognitive, or psychiatric illness causing inability to follow the study protocol: i.e. severe depression, anxiety, dementia, poor physical health with likely possibility of hospitalization within the next twelve weeks.
Planned hospitalization or surgery within the next twelve weeks
Participation in another clinical trial with a rehabilitation or exercise intervention
Inclusion Criteria:
Participants can be from any racial or ethnic origin. | Contradiction |
In total, across both cohorts of the primary trial, there were at least 2 patients with a fever. | Adverse Events 1:
Total: 2/6 (33.33%)
Febrile neutropenia * 1/6 (16.67%)
Neutropenia * 0/6 (0.00%)
Thrombocytopenia * 1/6 (16.67%)
Diarrhoea * 0/6 (0.00%)
Pyrexia * 0/6 (0.00%)
Thrombosis in device * 1/6 (16.67%)
Fatigue * 0/6 (0.00%)
Mucosal inflammation * 0/6 (0.00%)
Device deployment issue * 0/6 (0.00%)
Hepatocellular injury * 1/6 (16.67%)
Cholecystitis * 1/6 (16.67%)
Adverse Events 2:
Total: 2/6 (33.33%)
Febrile neutropenia * 1/6 (16.67%)
Neutropenia * 1/6 (16.67%)
Thrombocytopenia * 0/6 (0.00%)
Diarrhoea * 0/6 (0.00%)
Pyrexia * 0/6 (0.00%)
Thrombosis in device * 1/6 (16.67%)
Fatigue * 0/6 (0.00%)
Mucosal inflammation * 0/6 (0.00%)
Device deployment issue * 0/6 (0.00%)
Hepatocellular injury * 0/6 (0.00%)
Cholecystitis * 0/6 (0.00%) | Entailment |
We cannot compare results between the two Arms of the primary trial as there were no patients in cohort 1. | Outcome Measurement:
Maximum Tolerated Dose Determined by Dose-limiting Toxicities
1st 3 pts will be treated on arm 2. If 0/3 DLTs observed, the dose will be escalated to arm 3. If 1/3 DLTs onserved on arm 2, 3 more pts will be treated on arm 2. If no additional DLTs are observed on arm 2, the dose will be escalated to arm 3. If at most 1/6 DLTs observed on arm 3, arm 3 will be considered the MTD. If more than 1/6 DLTs observed on arm 3, the dose will be de-escalated to arm 2. If at most 1/6 DLTs observed on arm 2, arm 2 will be considered the MTD. If more than 1/6 pts on arm 2 experience a DLT, the dose will be de-escalated to arm 1. The remaining pts will be treated on arm 1 as the MTD, unless more than 1/6 DLTs, in which case the study will stop. DLT is defined as any grade III or IV non-hematologic toxicity (incl. diarrhea w\ adequate antidiarrheal treatment & hydration & nausea/vomiting w\ maximal antiemetic prophylaxis, as per protocol) or grade IV hematologic toxicity. DLT will be based on the 1st course of treatment according to the revised NCI CTC v 2.0
Time frame: 21 days
Results 1:
Arm/Group Title: Arm 1
Arm/Group Description: Capecitabine 800 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
Overall Number of Participants Analyzed: 0
Measure Type: Number
Unit of Measure: Patients experiencing DLT
Results 2:
Arm/Group Title: Arm 2
Arm/Group Description: Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
Overall Number of Participants Analyzed: 3
Measure Type: Number
Unit of Measure: Patients experiencing DLT 0 | Entailment |
Only one patient cohort of the primary trial had a positive median Insulin change from baseline. | Outcome Measurement:
Insulin
Insulin measured as percent change from baseline
Time frame: change from baseline to 6 months
Results 1:
Arm/Group Title: Metformin + Lifestyle Intervention
Arm/Group Description: Metformin: Week 1: 500 mg at dinner time Weeks 2-4: 1000 mg at dinner time Weeks 5+: 500 mg in morning; 1000 mg at dinner time
Lifestyle intervention: Telephone-based lifestyle intervention (dietary change and physical activity) for weight loss.
Overall Number of Participants Analyzed: 83
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change from baseline -21.8 (-29.7 to -13.0)
Results 2:
Arm/Group Title: Placebo + Lifestyle Intervention
Arm/Group Description: Placebo: Week 1: 1 pill at dinner time Weeks 2-4: 2 pills at dinner time Weeks 5+: 1 pill in morning; 2 pills at dinner time
Lifestyle intervention: Telephone-based lifestyle intervention (dietary change and physical activity) for weight loss.
Overall Number of Participants Analyzed: 83
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change from baseline -17.7 (-25.9 to -8.6) | Contradiction |
Cohort 2 of the primary trial had one more patient with Stable disease than cohort 1. | Outcome Measurement:
Clinical Benefit Rate (CR Plus PR Plus SD)
Complete response (CR) + partial response (PR) + stable disease (SD) using RECIST 1.0
CR = disappearance of all target lesions
PR = at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter
SD = neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for progressive disease
SD is defined as lack of disease progression by 24 weeks.
Time frame: 24 weeks after start of treatment
Results 1:
Arm/Group Title: Arm 1 (6 mg Estradiol)
Arm/Group Description: 6 mg of estradiol daily (2 mg tid).
Overall Number of Participants Analyzed: 34
Measure Type: Number
Unit of Measure: participants Complete response (CR): 0
Partial response (PR): 3
Stable disease (SD): 7
CR+PR+SD: 10
Results 2:
Arm/Group Title: Arm 2 (30 mg Estradiol)
Arm/Group Description: 30 mg of estradiol. (10 mg tid)
Overall Number of Participants Analyzed: 32
Measure Type: Number
Unit of Measure: participants Complete response (CR): 0
Partial response (PR): 1
Stable disease (SD): 8
CR+PR+SD: 9 | Entailment |
Left ventricular ejection fraction > 50% is required for participation in the primary trial. | LVEF 50% as measured by echocardiogram or MUGA scan | Entailment |
Patients with cancer in situ of the cervix are eligible for the primary trial and the secondary trial. | Exclusion Criteria:
History of cancer other than breast cancer within 5 years excluding basal/squamous cell skin carcinoma in situ of the cervix
Exclusion Criteria:
Any other malignancy in the last 5 years, except for basal cell cancer or cancer in situ of the cervix | Entailment |
the primary trial requires participants to have undergone PTR. | Inclusion Criteria:
Patients must have completed definitive resection of primary tumor with adequate excision of gross disease. | Entailment |
participants of cohort 1 in the primary trial and all participants of the secondary trial take 1 milligram of anastrozole and 40 milligrams of simvastatin PO QD. | INTERVENTION 1:
Arimidex Group
Anastrozole(ARIMIDEX): 1 mg once daily oral dose
INTERVENTION 1:
anastrozole : 1 milligram tablet PO QD for 14 days | Contradiction |
A female patient over the age of 18 suffering from chronic viral hepatitis would be eligible for the primary trial. | Inclusion Criteria:
Age 18 years or older
Exclusion Criteria:
Known chronic liver disease | Contradiction |
Women classified as high-risk of developing breast cancer within the next 5 years and within her lifetime by the Gail model are eligible for the primary trial. | Inclusion Criteria:
Gail risk >= 1.7% and/or relative risk >= 3 times that for 5-year age group | Entailment |
Cohort 1 of the primary trial recorded more optical adversse events than cohort 2. | Adverse Events 1:
Total: 61/202 (30.20%)
FEBRILE NEUTROPENIA 1/202 (0.50%)
LEUKOPENIA 0/202 (0.00%)
NEUTROPENIA 2/202 (0.99%)
CARDIAC FAILURE CONGESTIVE 0/202 (0.00%)
CARDIO-RESPIRATORY ARREST 1/202 (0.50%)
PERICARDIAL EFFUSION 1/202 (0.50%)
CATARACT 1/202 (0.50%)
OPTIC NEUROPATHY 0/202 (0.00%)
ABDOMINAL PAIN 0/202 (0.00%)
CONSTIPATION 0/202 (0.00%)
DIARRHOEA 5/202 (2.48%)
Adverse Events 2:
Total: 42/201 (20.90%)
FEBRILE NEUTROPENIA 0/201 (0.00%)
LEUKOPENIA 1/201 (0.50%)
NEUTROPENIA 0/201 (0.00%)
CARDIAC FAILURE CONGESTIVE 1/201 (0.50%)
CARDIO-RESPIRATORY ARREST 0/201 (0.00%)
PERICARDIAL EFFUSION 0/201 (0.00%)
CATARACT 1/201 (0.50%)
OPTIC NEUROPATHY 1/201 (0.50%)
ABDOMINAL PAIN 1/201 (0.50%)
CONSTIPATION 1/201 (0.50%)
DIARRHOEA 3/201 (1.49%) | Contradiction |
Less than 0.25% of patients in cohort 1 of the primary trial suffered from Hyperbilirrubinemia. | Adverse Events 1:
Hyperbilirrubinemia [1]1/436 (0.23%) | Entailment |
Patients with dementia or schizophrenia may be eligible for the primary trial and the secondary trial. | Inclusion Criteria:
Patients
with unilateral primary cancer pathologically confirmed before neoadjuvant chemotherapy (NAC)
who received NAC
with detectable lesion / clip marker on ultrasound
with cT1-T3 tumors
clinical and imaging complete or near-complete response on MRI
with informed consent
Exclusion Criteria:
Multifocal cancer
Residual microcalcification
Contralateral breast cancer
Concurrent serious uncontrolled medical disorder, | Contradiction |
the primary trial and the secondary trial use ECOG to evaluate potential candidates' performance status. | World Health Organization (WHO) performance status of 0, 1, or 2
Zubrod performance status less than 2 | Contradiction |
More than 5% of the primary trial participants achieved Objective Response (OR). | Outcome Measurement:
Objective Response (OR)
Objective response (OR) including complete response (CR) and partial response (PR) according to the Response Evaluation Criteria in Solid Tumours (RECIST) criteria .
Time frame: From first dose of study medication to response measurement, up to 34 month
Results 1:
Arm/Group Title: Afatinib 50 mg
Arm/Group Description: Patients received continuous daily dosing with Afatinib 50 mg therapy over 28-day treatment cycles until further disease progression or undue toxicity.
Overall Number of Participants Analyzed: 41
Measure Type: Number
Unit of Measure: Participants 4 | Entailment |
Every patient in the primary trial is given tipifarnib PO, along with paclitaxel, doxorubicin hydrochloride and acyclophosphamide IV, but only a subset of participants undergo axillary lymph node dissection. | INTERVENTION 1:
Arm I
See Detailed Description
tipifarnib: Given orally
paclitaxel: Given IV
doxorubicin hydrochloride: Given IV
cyclophosphamide: Given IV
pegfilgrastim: Given SC
conventional surgery: surgical procedures performed on patients
axillary lymph node dissection: correlative study | Contradiction |
None of the patients in the primary trial or the secondary trial committed suicide. | Adverse Events 1:
Total: 6
Atrial fibrillation 1/67 (1.49%)
Ventricular fibrillation 1/67 (1.49%)
Gastrointestinal perforation 1/67 (1.49%)
Periproctitis 1/67 (1.49%)
General physical health deterioration 1/67 (1.49%)
Escherichia sepsis 1/67 (1.49%)
Pneumonia 1/67 (1.49%)
Tumour pain 1/67 (1.49%)
Renal failure acute 1/67 (1.49%)
Pleurisy 1/67 (1.49%)
Adverse Events 1:
Total: 5/32 (15.63%)
Leukopenia 1/32 (3.13%)
Neutropenia 1/32 (3.13%)
Cataract 1/32 (3.13%)
Infection 1/32 (3.13%)
Upper respiratory tract infection 1/32 (3.13%)
Completed suicide 1/32 (3.13%) | Contradiction |
Stephanie has been living with her husband for 31 years, she is eligible for the primary trial. | Inclusion Criteria:
Has a partner or spouse who is > 21
Lives with a romantic partner > 6 months | Entailment |
All of the adverse events recorded in the primary trial were cardiac related. | Adverse Events 1:
Total: 5/45 (11.11%)
Neutrophils/granulocytes (ANC/AGC) * [1]0/45 (0.00%)
Neutrophils/granulocytes (ANC/AGC) * [2]0/45 (0.00%)
Diabetes decompensation * 0/45 (0.00%)
Diarrhea * [2]0/45 (0.00%)
Mucositis/stomatitis and Vomiting * [3]0/45 (0.00%)
Pancreatitis * [4]1/45 (2.22%)
Febrile neutropenia * [2]3/45 (6.67%)
Adverse Events 2:
Total: 0/46 (0.00%)
Neutrophils/granulocytes (ANC/AGC) * [1]0/46 (0.00%)
Neutrophils/granulocytes (ANC/AGC) * [2]0/46 (0.00%)
Diabetes decompensation * 0/46 (0.00%)
Diarrhea * [2]0/46 (0.00%)
Mucositis/stomatitis and Vomiting * [3]0/46 (0.00%)
Pancreatitis * [4]0/46 (0.00%)
Febrile neutropenia * [2]0/46 (0.00%)
Infection pulmonary/ Upper airway NOS * [5]0/46 (0.00%) | Contradiction |
Pre and Post menopausal women can enter the primary trial, as long as they do not have prior hormone replacement therapy. | Inclusion Criteria:
Female 18 + years of age
Confirmed diagnosis of DCIS on core or excisional/incisional biopsy and scheduled for definitive surgery
Pre or Post menopausal women reporting no use of hormone replacement therapy, tamoxifen or raloxifene within the prior 6 months to eligibility screening | Entailment |
the primary trial and the secondary trial are testing completely different modalities of interventions, but utilising the same 21 day cycle. | INTERVENTION 1:
Treatment (Tivantinib)
Patients receive tivantinib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC. Archived tumor tissue samples are also analyzed.
Laboratory Biomarker Analysis: Correlative studies
Tivantinib: Given PO
INTERVENTION 1:
Prone
Prone position
INTERVENTION 2:
Supine
Supine position | Contradiction |
Patients with ERBB2 positive tumors are eligible for the primary trial. | INCLUSION CRITERIA
erbB-2 gene amplified tumor (FISH or CISH) or erbB-2 overexpression (IHC 3+, or IHC2+ with FISH or CISH confirmation), based on local testing, or based on centralized FISH testing prior to day 1. | Entailment |
Most patients in the primary trial treated with Eribulin Mesylate did not achieve complete response (CR) or partial response (PR). | Outcome Measurement:
Objective Response Rate (ORR)
The ORR was defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Targeted lesions were assessed by computed tomography (CT) and magnetic resonance imaging (MRI) which were then assessed by the investigator based on RECIST. CR was defined as the disappearance of all target lesions. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters. Possible CR and PR had to be confirmed no fewer than 4 weeks after the initial response assessment. A brain and bone scan was performed by CT/MRI within 1 week after confirmation of a response to ensure no new metastases. To be assigned a status of CR or PR, changes in tumor measurements had to be confirmed by repeat evaluations, to be performed not fewer than 4 weeks after the response criteria were first met. ORR = CR + PR
Time frame: Cycle 1 (Day 1) until first evidence of disease progression, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years
Results 1:
Arm/Group Title: Eribulin Mesylate
Arm/Group Description: Eribulin mesylate at 1.4 mg/m^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
Overall Number of Participants Analyzed: 56
Measure Type: Number
Unit of Measure: Percentage of participants 28.6 | Entailment |
Patients with invasive breast cancer with a diameter of less than 4 cm are included in the primary trial. | Ipsilateral biopsy-proven invasive breast cancer <5 cm in maximal dimension by Ultrasound or Mammography. | Entailment |
Fiona's sister, who is 34 years old was diagnosed with a ductal carcinoma, therefore fiona may be eligible for the primary trial. | Inclusion Criteria
A first degree relative with breast cancer under the age of 60 or multiple second degree relatives with breast cancer. | Entailment |
For some adverse event types in the primary trial, there were no recorded cases. | Adverse Events 1:
Total: 6/8 (75.00%)
Thrombocytopenia 1/8 (12.50%)
Hypertension 1/8 (12.50%)
Hepatotoxicity 3/8 (37.50%)
Pancreatectomy * 1/8 (12.50%) | Contradiction |
Cohort 1 of the primary trial had more cases of Hepatic encephalopathy and Pneumonia than cohort 2. | Adverse Events 1:
Total: 5/26 (19.23%)
Febrile neutropenia 1/26 (3.85%)
Abdominal pain 0/26 (0.00%)
Constipation 0/26 (0.00%)
Nausea 1/26 (3.85%)
Pancreatitis 1/26 (3.85%)
Vomiting 2/26 (7.69%)
Pain 0/26 (0.00%)
Pneumonia 0/26 (0.00%)
Urinary tract infection 1/26 (3.85%)
Lumbar vertebral fracture 1/26 (3.85%)
Ammonia increased 1/26 (3.85%)
Hepatic encephalopathy 1/26 (3.85%)
Adverse Events 2:
Total: 4/13 (30.77%)
Febrile neutropenia 1/13 (7.69%)
Abdominal pain 1/13 (7.69%)
Constipation 1/13 (7.69%)
Nausea 0/13 (0.00%)
Pancreatitis 0/13 (0.00%)
Vomiting 0/13 (0.00%)
Pain 1/13 (7.69%)
Pneumonia 1/13 (7.69%)
Urinary tract infection 0/13 (0.00%)
Lumbar vertebral fracture 0/13 (0.00%)
Ammonia increased 0/13 (0.00%)
Hepatic encephalopathy 0/13 (0.00%) | Contradiction |
Patients with HER2 positive breast tumors are eligible for the primary trial, but excluded from the secondary trial. | Inclusion Criteria:
Breast cancer with evidence of unresectable, locally recurrent, or metastatic disease.
Tumors over-expressing Her-2
Candidate for treatment with docetaxel/trastuzumab
HER2-positive by fluorescence in situ hybridization (FISH) or immunohistochemistry 3+ staining confirmed in the adjuvant or metastatic setting | Contradiction |
The intervention for the primary trial does not require patients to undergo any medical treatment during the study, whereas in the secondary trial, all patients receive Radiation Therapy. | INTERVENTION 1:
Arm 1: BREASTChoice (Decision Tool)
Investigators recruited patients scheduled for a plastic/reconstruction consult. Investigators identified patients who completed a mastectomy, or were scheduled for one, and considering reconstruction, but didn't have an appointment with a plastic/reconstructive surgeon. A study team member called the patient to determine their interest and offered for them to come to their scheduled appointment 30 minutes early to meet a coordinator or offered them the option to complete pre-appointment procedures at home. Patients randomized using computer random assignment. If the patient didn't have an appointment, she scheduled a convenient time to complete study procedures with research staff. Patients interacted with the decision tool. They were asked to answer a survey. After the appointment, the team collected information consult duration, decision process quality, and measures of shared decision making. Patient participation was approximately 30 minutes.
INTERVENTION 2:
Arm 2: Enhanced Usual Care (Surgical Care Booklet)
Investigators recruited patients scheduled for plastic/reconstruction consultation. Investigators identified patients who completed or scheduled a mastectomy, and considering reconstruction, but didn't have an appointment with a plastic/reconstructive surgeon. A study team member called the patient to determine their interest and offered for them to come to their scheduled appointment 30 minutes early to meet a coordinator or to complete the pre-appointment procedures at home. Patients were randomized using computer random assignment. If the patient didn't have an appointment, she scheduled a convenient time to complete study procedures with research staff. Patients interacted with American Society of Plastic Surgeons booklet "Breast Reconstruction." They were asked to answer a survey. After the appointment, the team collected information about consult duration, decision process quality, and measures of shared decision making. Patient participation was approximately 30 minutes.
INTERVENTION 1:
ARM 1 Daily Boost
Radiation Therapy
Radiation Therapy: Arm 1= 15 daily radiation fractions of 2.7 Gy, Monday to Friday for 3 weeks, to the whole breast with a daily concomitant boost of 0.5 Gy to the tumor bed, for a total daily dose of 3.2 Gy to the tumor bed (2.7Gy+0.5 Gy). The overall dose will be 40.5 Gy to the breast and 48.0 Gy to the tumor bed.
Arm 2= 15 daily radiation fractions of 2.7 Gy Monday to friday for three weeks to the entire breast with a Friday boost of 2.0 Gy to the tumor bed, for a total dose to the tumor bed on each friday of 4.7 Gy (2.7 Gy+ 2.0 Gy). The overall dose will be 40.5 Gy to the breast and 46.5 gy to the tumor bed.
INTERVENTION 2:
ARM 2 Weekly Boost
Radiation Therapy
Radiation Therapy: Arm 1= 15 daily radiation fractions of 2.7 Gy, Monday to Friday for 3 weeks, to the whole breast with a daily concomitant boost of 0.5 Gy to the tumor bed, for a total daily dose of 3.2 Gy to the tumor bed (2.7Gy+0.5 Gy). The overall dose will be 40.5 Gy to the breast and 48.0 Gy to the tumor bed.
Arm 2= 15 daily radiation fractions of 2.7 Gy Monday to friday for three weeks to the entire breast with a Friday boost of 2.0 Gy to the tumor bed, for a total dose to the tumor bed on each friday of 4.7 Gy (2.7 Gy+ 2.0 Gy). The overall dose will be 40.5 Gy to the breast and 46.5 gy to the tumor bed. | Entailment |
Patients with cytologically confirmed breast cancer, who's Locally recurrent disease is amenable to radiation with curative intent are not eligible for the primary trial. | Inclusion Criteria:
Histologically or cytologically confirmed breast cancer that is either locally recurrent or metastatic.
Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent. | Entailment |
the primary trial does not have an intervention section. | INTERVENTION 1:
Study Participants
There are no arms or subgroups in this study. | Entailment |
the primary trial's intervention section does not describe the intervention dosage, frequency or duration for cohort 2, however cohort 1 recieves placebo twice daily for two months. | INTERVENTION 1:
Recruitment Population
Pre-randomization recruitment and enrollment | Contradiction |
the primary trial had a higher percentage of patients with at least partial response than either cohort of the secondary trial. | Outcome Measurement:
Number of Participants Who Had a Tumor Response, According to Standard RECIST (Response Evaluation Criteria in Solid Tumors) Criteria
Those who achieved either complete (disappearance of all target lesions) or partial (at least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD) response.
Time frame: Week 09, Week 18, at the end of each patient's treatment, and at 3, 6, 9, and 12 months after end of treatment.
Results 1:
Arm/Group Title: Caelyx, Docetaxel, Trastuzumab
Arm/Group Description: Stage 1: subjects will receive Caelyx one day every 3 weeks in combination with docetaxel one day every 3 weeks and trastuzumab once weekly during 6 cycles. At the end of this stage, based on the number of cardiac events, subjects will proceed to a second stage or restart with a lower dose of Caelyx.
Stage 2: subjects will be treated with the recommended dose of Caelyx (defined in the first stage) in combination with docetaxel and trastuzumab.
Overall Number of Participants Analyzed: 26
Measure Type: Number
Unit of Measure: Participants Participants who had a complete tumor response: 2
Participants who had a partial tumor response: 13
Participants who did not have a tumor response: 11
Outcome Measurement:
Objective Response Rate
Patient response rates will be measured by the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI. Responses include the following: Complete Response (CR) disappearance of all target lesions; Partial Response (PR) at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) best response from the start of treatment until disease progression.
Time frame: Baseline to 6 months
Results 1:
Arm/Group Title: Abraxane + Tigatuzumab
Arm/Group Description: Patients will receive Abraxane at 100 mg/m2 X 3 doses on Days 1, 8, and 15 at 28-day intervals and tigatuzumab to be administered as a 10 mg/kg loading dose followed by 5 mg/kg for the first cycle and then every other week on Days 1 and 15 for subsequent cycles. Patients will be evaluated for response every 8 weeks. Patients with disease progression will be taken off the study.
Overall Number of Participants Analyzed: 39
Measure Type: Number
Unit of Measure: percentage of patients 28 (14.9 to 45.0)
Results 2:
Arm/Group Title: Abraxane Alone
Arm/Group Description: Patients will receive Abraxane at 100 mg/m2 weekly X 3 doses on Days 1, 8, and 15 at 28-day intervals. Abraxane will be administered on an outpatient basis by an IV infusion over 30 minutes. Patients will be evaluated for response every 2 cycles (every 8 weeks).
Overall Number of Participants Analyzed: 21
Measure Type: Number
Unit of Measure: percentage of patients 38 (18 to 61.1) | Entailment |
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